While the above results are, at first, discouraging, it is also now clear that many of the issues associated with the anti-LPS IgM mAb trials likely reflect the difficult nature of this clinical indication (numerous other therapeutics have failed in sepsis and infectious disease trials) [153] as well as the specific characteristics of the natural, non-affinity-matured mAbs tested [124]. This evidence concerns the gene CD40LG and Sepsis.